The objective of this application is to investigate what roles mutations resulting in multidrug resistance play in human cancer. Such mutations are thought to limit successful chemotherapeutic treatment of advanced disease. The immediate aim is to develop sensitive and specific probes for detecting multidrug resistance cells in patient biopsies. This will be accomplished by generating monoclonal antibodies against the 170,000 dalton cell surface P-glucoprotein shown to be expressed in multidrug resistance cells. Heteroantisera against this protein already developed will be used to screen biopsy samples from cancer patients using the highly sensitive immunoblot (Western blot) procedure. DNA sequence specific for human P-glycoprotein will be cloned and used as probes for multidrug resistance mutations. Multidrug-resistant cell will be isolated in vitro from cell lines established from patient tumors. These will be studied and compared with resistant cells found in patients. This program should provide significant information concerning how drug-resistance limits chemotherapeutic treatment of malignancies. It may in addition, provide new vistas for improving therapeutic management.